An overdose of sulfonylureas may cause hypoglycaemia.
Moderate symptoms of hypoglycaemia, without any loss of consciousness or neurological signs, must be corrected by carbohydrate intake, dose adjustment and/or change of diet. Strict monitoring should be continued until the doctor is sure that the patient is out of danger.
Severe hypoglycaemic reactions, with coma, convulsions or other neurological disorders are possible and must be treated as a medical emergency, requiring immediate hospitalisation.
If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid I.V. injection of 50 ml of concentrated glucose solution (20 to 30%). This should be followed by continuous infusion of a more dilute glucose solution (10%) at a rate that will maintain blood glucose levels above 1 g/l. Patients should be monitored closely and, depending on the patient's condition after this time, the doctor will decide if further monitoring is necessary.
Dialysis is of no benefit to patients due to the strong binding of Gliclada to proteins.
Not applicable
Based on the experience with Gliclada, the following undesirable effects have to be mentioned.
Hypoglycaemia
As for other sulfonylureas, treatment with Gliclada can cause hypoglycaemia, if mealtimes are irregular and, in particular, if meals are skipped. Possible symptoms of hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and lethal outcome.
In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia.
Usually, symptoms disappear after intake of carbohydrates (sugar). However, artificial sweeteners have no effect. Experience with other sulfonylureas shows that hypoglycaemia can recur even when measures prove effective initially.
If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation are required.
Gastrointestinal disturbances, including abdominal pain, nausea, vomiting, dyspepsia, diarrhoea and constipation have been reported: if these should occur they can be avoided or minimised if Gliclada is taken with breakfast.
The following undesirable effects have been more rarely reported:
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis).
Blood and lymphatic system disorders: Changes in haematology are rare. They may include anaemia, leucopenia, thrombocytopenia, granulocytopenia. These are in general reversible upon discontinuation of Gliclada.
Hepatobiliary disorders: Raised hepatic enzyme levels (ASAT, ALAT, alkaline phosphatase), hepatitis (isolated reports). Discontinue treatment if cholestatic jaundice appears.
These symptoms usually disappear after discontinuation of treatment.
Eye disorders: Transient visual disturbances may occur, especially on initiation of treatment, due to changes in blood glucose levels.
Class attribution effects
As for other sulfonylureas, the following adverse events have been observed: cases of erythrocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatremia, elevated liver enzyme levels and even impairment of liver function (e.g. with cholestasis and jaundice) and hepatitis which regressed after withdrawal of the sulfonylurea or led to life-threatening liver failure in isolated cases.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard
Preclinical data reveal no special hazards for humans based on conventional studies of repeated dose toxicity and genotoxicity. Long term carcinogenicity studies have not been done. No teratogenic changes have been shown in animal studies, but lower fetal body weight was observed in animals receiving doses 9.4 fold higher than the maximum recommended dose in humans.
Pharmacotherapeuticgroup: sulfonamides, urea derivatives.
ATC code: A10BB09
Gliclada is a hypoglycaemic sulfonylurea antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.
Gliclada reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of treatment.
In addition to these metabolic properties, Gliclada has haemovascular properties.
Effects on insulin release
In type 2 diabetics, Gliclada restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin response is seen in response to stimulation induced by a meal or glucose.
Haemovascular properties:
Gliclada decreases microthrombosis by two mechanisms which may be involved in complications of diabetes:
- a partial inhibition of platelet aggregation and adhesion, with a decrease in the markers of platelet activation (beta thromboglobulin, thromboxane B2),
- an action on the vascular endothelium fibrinolytic activity with an increase in tPA activity.
The drug is well absorbed and its half-life in man is approximately 10-12 hours. Gliclada is metabolised in the liver; less that 5% of the dose is excreted unchanged in the urine.
Gliclada has no known influence on the ability to drive and use machines. However, patients should be informed that their concentration may be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment.
No special requirements.
